GREEN AGRICULTURE AND BLUE WATER IN CHINA: REINTEGRATING CROP AND LIVESTOCK PRODUCTION FOR CLEAN WATER

• AGD aims for a green environment, sustainable agriculture and clean water. • Presenting examples of the impact of agriculture on water quality. • Presenting examples of solutions for sustainable agriculture and improved water quality. • Integration of livestock and cropping systems is possible on a farm or among farms. • Providing recommendations for further development of sustainable agriculture. Crop and livestock production are essential to maintain food security. In China, crop and livestock production were integrated in the past. Today, small backyard systems are still integrated but the larger livestock farms are landless and largely geographically separated from crop production systems. As a result, there is less recycling of animal manures and there are lower nutrient use efficiencies in the Chinese food production systems. This, in turn, results in considerable losses of nutrients, causing water pollution and harmful algal blooms in Chinese lakes, rivers and seas. To turn the tide, there is a need for agricultural “green” development for food production through reintegrating crop and livestock production. An additional wish is to turn the Chinese water systems “blue” to secure clean water for current and future generations. In this paper, current knowledge is summarized to identify promising interventions for reintegrating crop and livestock production toward clean water. Technical, social, economic, policy and environmental interventions are addressed and examples are given. The paper highlights recommended next steps to achieve “green” agriculture and “blue” water in China.     

NUTRIENT USE EFFICIENCY AND LOSSES OF INDUSTRIAL FARMS AND MIXED SMALLHOLDINGS: LESSONS FROM THE NORTH CHINA PLAIN

• Degree of integration of crop and livestock was insufficient on mixed smallholdings. • Liquid manure discharges on industrial farms hamper the closing of nutrient loops. • Coupling with local crop farms is encouraged to achieve integration of crop-livestock systems. The proportion of industrial livestock in China has increased over the past 30 years, which increases animal performance but causes the decoupling of crop and livestock production. Here, we aimed to quantify nutrient flows, nutrient use efficiency, and nutrient losses in different livestock systems in the North China Plain based on the NUFER-farm model. Activity data were collected by face-to-face surveys on pig and dairy (41 livestock farms) during 2016–2018. The two systems included industrial farms and mixed smallholdings. In mixed smallholdings, 4.0% and 9.6% of pig and dairy feed dry matter (DM) were derived from household farmland, but 4.8% and 9.3% of manure DM recycled to household farmland. Nutrient use efficiency in industrial farms was higher than in mixed smallholdings at animal level, herd level, and system level. To produce 1 kg N and P in animal products, nutrient losses in industrial pig farms (2.0 kg N and 1.3 kg P) were lower than in mixed pig smallholdings, nutrient losses in industrial dairy farms (2.7 kg N and 2.2 kg P) were slightly higher than in mixed dairy smallholdings. Liquid manure discharge in industrial farms was the main losses pathway in contrast to mixed smallholdings. This study suggests that feed localization can reduce nutrient surpluses at the district level. It is necessary to improve manure management and increase the degree of integrated crop-livestock in smallholdings. In industrial farms, it is desirable to increase the liquid manure recycling ratio through cooperating livestock and crop production at the district level.     

POLICIES AND REGULATIONS FOR PROMOTING MANURE MANAGEMENT FOR SUSTAINABLE LIVESTOCK PRODUCTION IN CHINA: A REVIEW

• Manure utilization is hindered by separate specialist crop and livestock production systems. • Improving manure utilization requires organizations for manure exchange. • Policies and action plans for improving manure utilization are critically reviewed. • A manure chain approach with third-party contractors is recommended. Livestock numbers in China have more than tripled between 1980 and 2017. The increase in the number of intensive livestock production systems has created the challenges of decoupled crop and livestock systems, low utilization of manures in croplands, and subsequent environmental pollution. Correspondingly, the government has enacted a series of policies and regulations to increase the sustainability of livestock production. This paper reviews the objectives of these policies and regulations and their impacts on manure management. Since 2017 there have been two policy guides to speed up the appropriate use of manures, three action plans for increasing manure recycling, and one technical guide to calculate nutrient balances. Requirements of manure pollution control and recycling for improved environmental performance of livestock production systems were included in three revised environmental laws. Most recent survey data indicate that the utilization of livestock manures was 70% in 2017, including that used as fertilizer and/or for production of energy. The targets for manure utilization are 75% in 2020 and 90% in 2035. To achieve these targets and promote ‘green livestock production’, additional changes are needed including the use of third-party enterprises that facilitate manure exchange between farms and a more integrated manure nutrient management approach.     

INTEGRATED CROP-LIVESTOCK SYSTEMS: LESSONS FROM NEW YORK,BRITISH COLUMBIA,AND THE SOUTH-EASTERN UNITED STATES

• Livestock production in North America has moved to fewer farms with greater inventories • Land application of livestock manures is a preferred nutrient recycling strategy • Confined animal feeding operations have challenges to utilize livestock manure sustainably • Integration of livestock and cropping systems is possible on a farm or among farms • Nutrient balance is needed for environmental sustainability Livestock production in the United States (US) and Canada is diverse, but shows a common trend in most livestock sectors toward fewer farms producing the majority of animal products despite a large number of farms still small in production scale. The migration to larger and more concentrated animal feeding operations in beef finishing and poultry, swine, and dairy production allows processors to streamline supplies to meet market demand for abundant, low-cost livestock products, whether that be for packaged meat, dairy products, or eggs. With concentration of livestock operations comes the challenge of managing manures. When sufficient land is available and nutrients are needed, livestock manure is an excellent nutrient source and land application is the preferred method of recycling this resource. However, when livestock production is constrained in a geographical area and animal densities are high, manure may become an environmental liability with potentially greater risk for runoff and leaching of nutrients, emission of odors, ammonia, and greenhouse gases, and release to the environment of pathogens and chemicals of emerging concern. Addressing these challenges now and into the future requires learning from mistakes and adopting successful approaches. We describe different levels of integration between livestock and crop producers in New York, British Columbia, and the south-eastern US as learning opportunities to improve economic and environmental sustainability. Examples show that effective solutions should recognize (1) manure has value and is not just a cost, (2) farmers, farm advisors, extension educators, nutrient management planners, crop advisors, nutritionists, state agency personnel, regulators, and university researchers need to be active participants in development of solutions, and (3) change to a sustainable future requires a combination of government regulation and outcome-based incentives.     

INTENSIFICATION OF GRASSLAND-BASED DAIRY PRODUCTION AND ITS IMPACTS ON LAND,NITROGEN AND PHOSPHORUS USE EFFICIENCIES

• Monitoring data of>5000 dairy farms collected and examined in uniform manner. • Environmental performances of farms influenced by government regulations. • N and P surpluses at farm level remained about constant with intensity level. • N and P use efficiencies at farm, herd and soil increased with intensity level. • Accounting for externalization of off-farm feed production affects NUE and PUE. • Ammonia emissions per kg milk decreased with the level of intensification. Many grassland-based dairy farms are intensifying production, i.e., produce more milk per ha of land in response to the increasing demand for milk (by about 2% per year) in a globalized market. However, intensive dairy farming has been implicated for its resources use, ammonia and greenhouse gas emissions, and eutrophication impacts. This paper addresses the question of how the intensity of dairy production relates to N and P surpluses and use efficiencies on farms subjected to agri-environmental regulations. Detailed monitoring data were analyzed from 2858 grassland-based dairy farms in The Netherlands for the year 2015. The farms produced on average 925 Mg·yr⁻¹ milk. Milk production per ha ranged from<10 to>30 Mg·ha⁻¹·yr⁻¹. Purchased feed and manure export strongly increased with the level of intensification. Surpluses of N and P at farm level remained constant and ammonia emissions per kg milk decreased with the level of intensification. In conclusion, N and P surpluses did not differ much among dairy farms greatly differing in intensity due to legal N and P application limits and obligatory export of manure surpluses to other farms. Further, N and P use efficiencies also did not differ among dairy farms differing in intensity provided the externalization of feed production was accounted for. This paper provides lessons for proper monitoring and control of N and P cycling in dairy farming.     

LAND-USE INTENSIFICATION TRENDS IN THE RIO DE LA PLATA REGION OF SOUTH AMERICA: TOWARD SPECIALIZATION OR RECOUPLING CROP AND LIVESTOCK PRODUCTION

• Current intensification trends in the Rio de la Plata need urgent re-direction.•Integrated crop-livestock systems reconcile food production with ecosystem services.•Case studies validate recoupling as a sustainable way to ecological intensification.The Rio de la Plata region comprises central Argentina, Uruguay, and southern Brazil. Modern agriculture developed around 1900 with recent decades being characterized by the advance of cropping areas over native grasslands. Highly specialized agriculture has decoupled crop and livestock production but has succeeded in intensifying yields. However, significant losses of ecosystem services have been reported. Thus, questions have been raised on the sustainability of this pathway. A glance at world regions that have experienced similar trends suggests that an urgent course correction is needed. A major concern has been the lack of diversity in regions with highly specialized agriculture, promoting renewed interest in integrated crop-livestock systems (ICLS), not only because ICLS are more diverse than specialized systems, but also because they are rare examples of reconciliation between agroecosystem intensification and environmental quality. Consequently, this paper discusses alternatives to redesign multifunctional landscapes based on ICLS. Recent data provide evidence that recoupling crop and animal production increases the resilience of nutrient cycling functions and economic indicators to external stressors, enabling these systems to face climate-market uncertainty and reconcile food production with the provision of diverse ecosystem services. Finally, these concepts are exemplified in case studies where this perspective has been successfully applied.     

NEW ZEALAND DAIRY FARM SYSTEMS AND KEY ENVIRONMENTAL EFFECTS

• NZ dairy farming systems are based on year-round grazing of perennial pasture (ryegrass/white clover). • Milk production per hectare has increased by about 29% with increased use of externally-sourced feeds over the last two decades. • Externally-sourced feeds with a low protein concentration can potentially reduce N₂O emissions and N leaching per unit of production. • Systems analysis is important for evaluating mitigations to minimize trade-offs between environmental impacts. This paper provides an overview of the range of dairy pasture grazing systems used in New Zealand (NZ), the changes with increased inputs over time and associated key environmental effects including nitrogen (N) leaching and greenhouse gas (GHG) emissions. NZ dairy farming systems are based on year-round grazing and seasonal milk production on perennial ryegrass/clover pasture where cows are rotationally grazed in paddocks. There was an increase in stocking rate on NZ dairy farms from 2.62 cows ha⁻¹ in 2000/2001 to 2.84 cows ha⁻¹ in 2015/2016. During the same period annual milk solids production increased from 315 to 378 kg·yr⁻¹ per cow. This performance has coincided with an increase in N fertilizer use (by ~ 30%) and a twofold increase in externally-sourced feeds. Externally-sourced feeds with a low protein concentration (e.g., maize silage) can increase the efficiency of N utilization and potentially reduce N losses per unit of production. Off-paddock facilities (such as standoff or feed pads) are often used to restrict grazing during very wet winter conditions. A systems analysis of contrasting dairy farms in Waikato (largest NZ dairying region) indicates that the increased input would result in an increase in per-cow milk production but little change in efficiency of milk production from a total land use perspective. This analysis also shows that the increased inputs caused an 11% decrease in N footprint (i.e., N emissions per unit of milk production) and a 2% increase in C footprint (i.e., greenhouse gas (GHG) emissions per unit of milk production).     

REINTEGRATION OF CROP-LIVESTOCK SYSTEMS IN EUROPE: AN OVERVIEW

• ICLS combines the benefits of specialization with increased resilience of the system.• Clear opportunities but also barriers for ICLS were observed.• ICLS need to be embedded within future environmental legislation.• ICLS systems with a range of intensities are needed to support a biodiverse landscape.Ongoing specialization of crop and livestock systems provides socioeconomic benefits to the farmer but has led to greater externalization of environmental costs when compared to mixed farming systems. Better integration of crop and livestock systems offers great potential to rebalance the economic and environmental trade-offs in both systems. The aims of this study were to analyze changes in farm structure and review and evaluate the potential for reintegrating specialized intensive crop and livestock systems, with specific emphasis on identifying the co-benefits and barriers to reintegration. Historically, animals were essential to recycle nutrients in the farming system but this became less important with the availability of synthetic fertilisers. Although mixed farm systems can be economically attractive, benefits of scale combined with socio-economic factors have resulted in on-farm and regional specialization with negative environmental impacts. Reintegration is therefore needed to reduce nutrient surpluses at farm, regional and national levels, and to improve soil quality in intensive cropping systems. Reintegration offers practical and cost-effective options to widen crop rotations and promotes the use of organic inputs and associated benefits, reducing dependency on synthetic fertilisers, biocides and manure processing costs. Circular agriculture goes beyond manure management and requires adaptation of both food production and consumption patterns, matching local capacity to produce with food demand. Consequently, feed transport, greenhouse gas emissions, nutrient surpluses and nutrient losses to the environment can be reduced. It is concluded that reintegration of specialized farms within a region can provide benefits to farmers but may also lead to further intensification of land use. New approaches within a food system context offer alternatives for reintegration, but require strong policy incentives which show clear, tangible and lasting benefits for farmers, the environment and the wider community.     

PORK PRODUCTION SYSTEMS IN CHINA: A REVIEW OF THEIR DEVELOPMENT,CHALLENGES AND PROSPECTS IN GREEN PRODUCTION

•Large-scale industrial pork production enterprises are preferred in China in the future.•Challenges to green pork production include emissions, feed shortage and residues.•Potential solutions to green production include precise feeding and manure recycling.This paper reviews the changes in pork production in China, the largest pork producing and consuming nation in the world. The pork sector in China has changed dramatically since the 1990s, with large-scale intensive pork production systems replacing the former, exclusively family-based pork production systems. Modern breeding, feeding, vaccinating, and management technologies are widely used now. However, smallholders still account for a large proportion of the total production. The intensification and specialization of the pork sector is expected to continue in the future, but there is increasing awareness and pressure to develop more environmentally-sustainable production systems. The relative shortage of domestically produced feed, the low utilization efficiency of feed ingredients, the large emissions of nitrogen and phosphorus to the environment, the high use of antibiotics, and the presence of residual metals in manures are very large challenges for the pork sector nowadays. To solve these problems, techniques including new feed resource utilization, precise feeding, low-protein diets, alternatives to antibiotics and increased manure recycling are all important topics and research directions today. With new techniques and management approaches, it is possible to build more sustainable pork production systems in China.     

EGG PRODUCTION IN CHINA: CURRENT STATUS AND OUTLOOK

• China is now the largest egg production country worldwide• Egg production in China is characterized by diversity in several aspects• China is now capable of breeding new varieties, with more than 50% of the market share• Policies have been implemented to ensure sustainable development of egg production• Integrating crop-chicken-vegetable production system is establishedEggs are one of the most nutritious and affordable animal products worldwide. From 1985, egg production in China has retained the leading place in the world. A total of 33 Mt of eggs were produced in 2019 representing ˃ 40% of the world total production. Egg production in China is characterized by diversity in several aspects, including layer breeds, products and production systems. New breeds and synthetic lines are developed to improve the genetic potentials of egg production and feed efficiency of layers. In the past, layer farms were run mostly by small households with 100 to 1000 layers per farm. Over the past decades, egg production in China has developed toward standardization and expansion of production systems, and many of these modern intensive farms raise millions of layers. Although the Chinese egg products maintain strong competitiveness over other animal products and imported egg products, the egg industry will grow at a slower pace compared to the past. Chinese consumers are more concerned about the quality and safety of eggs and egg products, as well as the environmental issues related to animal production, which presents challenges for the Chinese egg industry.     

COMPARISON OF POMELO (CITRUS MAXIMA) GROWN IN CHINA AND THAILAND

• China is the largest producer of pomelo globally. • Chinese pomelos are adapted to subtropical climates and Thai pomelos to tropical climates. • Guanxi pomelo is a popular cultivar in China and Thong Dee is the most popular in Thailand. • Naringin is the most abundant flavonoid in Chinese and Thai pomelos. • Fruity, sweet, sour, juicy and overall flavor attributes are important in consumer preference. Pomelo is a member of the genus Citrus that is a key contributor to the breeding of modern citrus cultivars. China is the largest producer of pomelo and one of the top five pomelo exporting countries. Pomelos from Thailand are also well-known for their excellent quality and flavor and are ranked in the top ten export countries. This review introduces pomelo planting locations and conditions in China and Thailand. The characteristics and qualities of some commercial pomelo cultivars in China and Thailand are summarized to introduce them to international consumers and to document their similarities and dissimilarities. Data on bioactive compounds and antioxidant capacity are also included for most Chinese and Thai pomelos to highlight how they differ in this aspect because consumers are increasingly interested in healthier foods. In addition, the sensory perception in terms of aroma, flavor, texture and taste attributes and consumer perspective and preferences are discussed.     

BIOINSECTICIDES AS FUTURE MAINSTREAM PEST CONTROL AGENTS: OPPORTUNITIES AND CHALLENGES

•Wide use of botanical insecticides is limited by the availability of certain plants. •Studies are needed to improve RNAi efficiency and to assess their safety risk. •Microbial insecticides are promising, but they only control a narrow range of pests. •Multitarget approach should be a promising strategy in future pest control. •Nanoformulation could enhance stability and control the release of bioinsecticides. Bioinsecticides are naturally-occurring substances from different sources that control insect pests. Ideal bioinsecticides should have low toxicity to non-target organisms. They should also be easily degraded in sewage treatment works and natural environments, highly effective in small quantities and affect target pests only. Public concerns about possible side-effects of synthetic pesticides have accelerated bioinsecticide research and development. However, to develop bioinsecticides into mainstream products, their high production costs, short shelf-life and often uncertain modes of action need to be considered. This review summarizes current progress on bioinsecticides which are categorized as biochemical insecticides and their derivatives, plant-incorporated protectants, and microbial bioinsecticides. The current constraints that prevent bioinsecticides from being widely used are discussed and future research directions are proposed.     

COMPARING PERFORMANCE OF CROP SPECIES MIXTURES AND PURE STANDS

•The literature on intercropping comprises thousands of papers. •Evidence synthesis is needed to develop general conclusions. •Quantitative evidence synthesis requires meaningful comparative performance metrics. •The background, meaning, and limitations of some performance metrics is explained. •Future challenges are identified. Intercropping is the planned cultivation of species mixtures on agricultural land. Intercropping has many attributes that make it attractive for developing a more sustainable agriculture, such as high yield, high resource use efficiency, lower input requirements, natural suppression of pests, pathogens and weeds, and building a soil with more organic carbon and nitrogen. Information is needed which species combinations perform best under different circumstances and which management is suitable to bring out the best from intercropping in a given production situation. The literature is replete with case studies on intercropping from across the globe, but evidence synthesis is needed to make this information accessible. Meta-analysis requires a careful choice of metric that is appropriate for answering the question at hand, and which lends itself for a robust meta-analysis. This paper reviews some metrics that may be used in the quantitative synthesis of literature data on intercropping.     

ROUTE DEVELOPMENT,ANTIVIRAL STUDIES,FIELD EVALUATION AND TOXICITY OF AN ANTIVIRAL PLANT PROTECTANT NK0238

• Developed a two-step synthetic route to anti-plant-virus candidate NK0238. • NK0238 exhibited a broad antivirus spectrum in greenhouse. • NK0238 showed comparable antivirus activities as controls in field trials. • NK0238 was safe to birds, fish, bees and silkworms. • NK0238 has a very good prospect in commercial development. It has previously been shown that tryptophan, the biosynthesis precursor of Peganum harmala alkaloids, and its derivatives have anti-TMV activity both in vitro and in vivo. Further exploration of this led to the identification of NK0238 as a highly effective agent for the prevention and control of diseases caused by plant viruses, but the existing routes are unsuitable for its large-scale synthesis. This study optimized a route for two-step synthesis of this virucide candidate via reaction of l-tryptophan with triphosgene to produce l-tryptophan-N-carboxylic anhydride, which then reacts with n-octylamine to give NK0238 at up to 94% yield and nearly 97% HPLC purity. In addition, the route was used for the preparation of NK0238 on a>40 g scale permitting further assessment of its antivirus activity in the greenhouse and field experiments, and toxicity tests. NK0238 exhibited useful antiviral activities against a variety of viruses both in greenhouse and field experiments. The toxicity tests showed that NK0238 was not acutely toxic to birds, fish, honey bees and silkworms. The optimized route provides a solid foundation for its large-scale synthesis and subsequent efficacy and toxicity studies, its excellent activity and safety make NK0238 a promising drug candidate for further development.     

WHEAT STRIPE RUST AND INTEGRATION OF SUSTAINABLE CONTROL STRATEGIES IN CHINA

• Stripe rust caused substantial yield losses in China. • P. striiformis is highly variable and the change from avirulence to virulence. • Different comprehensive control strategies were adopted in different epidemic region. Stripe (yellow) rust caused by Puccinia striiformis f. sp. tritici occurs in almost all wheat-producing regions of the world. Severe countrywide epidemics in China have caused substantial yield losses. Growing resistant cultivars is the best strategy to control this disease but the pathogen can overcome resistance in wheat cultivars. The high variation in the virulence of the pathogen combined with the large areas of susceptible wheat cultivars enables the pathogen population to increase rapidly and disperse over long distances under favorable environmental conditions, resulting in severe pandemics within cropping seasons. Current stripe rust control measures are based on many years of research including the underlying epidemiology regarding year-to-year survival of the pathogen, pathways of pathogen dispersal within seasons and years, the role of P. striiformis sexual hybridization, the use of resistance sources in breeding programs, and year-round surveillance of national wheat crops that are present in different parts of the country throughout the year. All these strategies depend on accurate prediction of epidemics, more precise use of fungicides to meet national requirements and better deployment of resistance genes. New ideas with potential application in sustainable protection of stripe rust include negative regulatory gene editing, resistance gene overexpression and biological control based on microbiomes.     

EXTRACTION AND EVALUATION OF EDIBLE OIL FROM SCHIZOCHYTRIUM SP. USING AN AQUEOUS ENZYMATIC METHOD

• Aqueous enzymatic extraction (AEE) is performed for oil extraction from Schizochytrium sp. • AEE process is optimized by response surface methodology. • Microalgal oil extracted by AEE has high contents of PUFA, tocopherols and phenolics. • AEEO exhibits considerable antioxidant activity as compared with SEO. Schizochytrium sp., a marine microalga, is a potential source of edible oil due to its short growth cycle and rapid lipid accumulation, especially of docosahexaenoic acid. An approach to isolate edible microalgal oil from Schizochytrium sp. using aqueous enzymatic extraction (AEE) was developed. Parameters were optimized by single-factor experiments followed by Box-Behnken design. Proteases were effective in extracting oil. The maximum free oil recovery (49.7%±0.58%) and total oil recovery (68.1%±0.94%) were obtained under optimum conditions of liquid-to-solid ratio of 4.8:1, a 2.5% enzyme concentration of papain and an extraction time of 2.2 h. There was a significant difference (P<0.05) in polyunsaturated fatty acid composition between microalgal oil obtained by AEE and by Soxhlet extraction, with the former having superior physiochemical properties and higher concentrations of bioactive components including total phenolic compounds and total tocopherols. These findings indicate a potential application of AEE for extraction of oil from Schizochytrium sp.     

A CASE FOR ASSESSING ALLOCASUARINA AND CASUARINA SPP. FOR USE IN AGROECOSYSTEM IMPROVEMENT IN SEMI-ARID AREAS WITH A FOCUS ON CENTRAL ANATOLIA,TURKEY

• Semi-arid ecosystems have been especially impacted by a long history of clearing, cropping and intensified grazing. • Selection of tree species for assessment for agroforestry needs to consider their utility and effectiveness in provision of ecosystem service, but also the wider consideration of preserving biodiversity. • Imperatives of agroecosystem services and biodiversity conservation (or restoration) will impact on species selection for agroforestry. • The potential of Allocasuarina and Casuarina for wider economic and ecosystem needs an endeavor to achieve demonstrable gains. Agroecosystems in water-limited contexts— Mediterranean, semi-arid and arid climatic zones—are too frequently degraded systems that will not provide the needed ecosystem services to ensure a future of sustainable agricultural production. The processes that have created this situation continue and are being accelerated by anthropogenic climate change. Increasing arboreal vegetation in these areas through agroforestry is an important strategy to conserve and improve their agroecosystems. Actinorhizal trees and shrubs in the Casurinaceae have a unique set of adaptations for heat and water stress, and/or infertile to hostile soils. Central Anatolia, Turkey is particularly at risk of increasing aridity and further degradation. Therefore, species of Allocasuarina and Casuarina have been evaluated for their potential use in agroecosystem improvement in semi-arid areas with a focus on Central Anatolia. Based on a semiquantitative environmental tolerance index and reported plant stature, eight species were identified as being of high (A. verticillata and C. pauper) to moderate (A. acutivalvis, A. decaisneana, A. dielsiana, A. huegeliana, C. cristata and C. obesa) priority for assessment, with none of these species having been adequately evaluated for agroforestry deployment in semi-arid agroecosystems in any context.     

DISCOVERY OF TRIKETONE-QUINOXALINE HYBRIDS AS POTENT HPPD INHIBITORS USING STRUCTURE-BASED DRUG DESIGN

• HPPD is one of the most promising targets for new herbicides. • A family of novel HPPD inhibitors based on the triketone-quinoxaline scaffold was designed and synthesized. • One particular product (7d) gave the highest inhibition of HPPD of the newly synthesized derivatives. • Triketone-quinoxaline derivatives provide a useful molecular scaffold for the discovery of novel HPPD-inhibiting herbicides. p-Hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27, HPPD) belongs to the family of Fe(II)-dependent non-heme oxygenases that occur in the majority of aerobic organisms. HPPD has proved to be a promising target in herbicide research and development. A battery of novel triketone-quinoxaline compounds has been designed using a structure-based drug design strategy and then prepared. Enzyme inhibition assays show that these synthesized derivatives possess favorable inhibition capability against Arabidopsis thaliana HPPD with IC₅₀ values ranging from 0.317 to 0.891 μmol·L⁻¹. Subsequently, the molecular docking results indicate that two adjacent carbonyls of the triketone moiety of the representative compound 2-(2,3-dimethyl-8-(o-tolyl)quinoxaline-6-carbonyl)-3-hydroxycyclohex-2-en-1-one (7d) engage in chelation with the ferrous ion of A. thaliana HPPD in a bidentate pose, and its quinoxaline scaffold forms two sets of parallel π-stacking interaction between two phenylalanine residues (Phe424 and Phe381). In addition, the extended phenyl group also interacts with Phe392 in a π-π stacking way. This study indicates that triketone-quinoxaline is a promising scaffold for discovering HPPD inhibitors with substantially increased potency, providing insight into the molecular design of new herbicides.